PHYSIOLOGY OF RETINAL PERICYTES

描述(改编自申请者摘要)：远距离 目的是为了刻画其功能的机制。 视网膜周细胞在病理生理条件下发生改变。 周细胞是包裹微血管的细胞，是人们感兴趣的细胞。 因为它们似乎可以调节视网膜内的血液流动 毛细血管。另一个令人感兴趣的事实是，选择性地失去 周细胞是糖尿病患者最早的组织病理学发现之一。 视网膜病变。该项目的一个前提是，分子中的 微环境调节周细胞的生理。这个 调查人员一直专注于金融危机破裂的后果 血-视网膜屏障，因为这种屏障的缺陷通常发生在 重要的威胁视力的疾病，如糖尿病。这项研究 策略的前提是离子通道在 周细胞功能。研究人员推测，离子的活动 当血浆来源的分子改变周细胞表达的通道时 在血-视网膜屏障的部位从血管系统渗漏 已经妥协了。为了解决这些问题，他们开发了一种 应用膜片钳技术的实验准备 细胞膜上离子通道活性的分析 新鲜从人和动物的视网膜上分离出来的血管。在预赛中 研究发现，等离子体可以激活几种类型的离子 视网膜周细胞中的通道。为了澄清通过哪些机制 来自血管系统的分子调节周细胞的功能， 该项目将解决以下具体目标。(1)定性 当视网膜周细胞被激活时，其活性改变的离子通道 暴露在血浆中；(2)检验胰岛素样生长的假设 胰岛素样生长因子-1(IGF-1)是一种由血浆衍生的调节分子。 视网膜周细胞中离子通道的功能；以及(3)检测 假设等离子体对离子通道的激活源于 分子，如胰岛素样生长因子-1，与血管活性增加密切相关。 周细胞内钙的浓度。从长远来看， 了解周细胞对病理反应的机制 生理条件将有助于制定治疗策略 维持视网膜周细胞的功能和存活 糖尿病视网膜病变等疾病。

DESCRIPTION (Adapted from applicant's abstract): The long-range objective is to characterize the mechanisms by which the function of retinal pericytes is altered under pathophysiological conditions. Pericytes, the cells which ensheathe the microvessels, are of interest since they appear to regulate the flow of blood within retinal capillaries. Also of interest is the fact that the selective loss of pericytes is one of the first histopathological findings in diabetic retinopathy. A premise of the project is that molecules in the microenvironment regulate the physiology of the pericyte. The investigators have focused on the consequences of a breakdown in the blood-retinal barrier since defects in this barrier occur commonly in important sight-threatening disorders such as diabetes. The research strategy is based on the premise that ion channels play a vital role in pericyte function. The investigators postulate that the activity of ion channels expressed by pericytes is altered when plasma-derived molecules leak from the vascular system at sites where the blood-retinal barrier is compromised. To address these issues, they have developed an experimental preparation in which the patch-clamp technique is used to analyze the activity of ion channels in pericytes located on micro- vessels freshly isolated from human and animal retinas. In preliminary studies, they discovered that plasma activates several types of ion channels in retinal pericytes. To clarify the mechanisms by which molecules from the vascular system regulate the function of pericytes, this project will address the following specific aims. (1) characterize the ion channels whose activities are altered when retinal pericytes are exposed to plasma; (2) test the hypothesis that insulin-like growth factor (IGF-1) is one of the plasma-derived molecules which regulates the function of ion channels in retinal pericytes; and (3) test the hypothesis that the activation of ion channels by plasma-derived molecules, such as IGF-1, is closely associated with an increase in the concentration of calcium within the pericyte. Over the long term, understanding the mechanisms by which pericytes respond to patho- physiological conditions will help in devising therapeutic strategies for maintaining the function and survival of pericytes in retinal disorders such as diabetic retinopathy.